Investigation of the behavioral and physiological consequences of treatment with monoamine oxidase inhibiting antidepressants have revealed a clear temporal dissociation between the rapid development of enzyme inhibition and the delayed onset of the remission of depressive symptoms, the precipitation of hypomanic or manic episodes and reductions in rapid-eye movement sleep and in blood pressure. Significant associations between orthostatic blood pressure changes and antidepressant effects, together with evidence that central Alpha-adrenergic receptor changes (as assessed by cardiovascular responses to clonidine) are also delayed, suggest that adaptive alterations in brain noradrenergic function may be an important mechanism in the therapeutic actions of these drugs. In other studies, baseline growth hormone elevations in response to clonidine administration were found to be significantly blunted in depressed patients compared to sex- and age-matched controls, suggesting the possibility of a primary abnormality in the noradrenergic system in these patients.